T4 Bacteriophage-Mediated Inhibition of Adsorption and Replication of Human Adenovirus in vitro

Abstract

T4 phage can inhibit infections by HAdV-5 of target cells. Our results suggest that T4 might be considered a novel agent against HAdV and possibly other pathogenic viruses. Potential antiviral effects of other phages should also be investigated.

Inhibitory Effects of Bacteriophage Preparations on Adenoviral Replication

“…In in vitroexperiments, both phage preparations reduced infectious titer of HAdV-5 in a dose-dependent manner, which provided the basis for the estimation of ED 50 , calculated for each type of experiment separately. Phage antiviral effect was observed first in our previous study [10], where T4 phage significantly reduced HAdV-5 titer.…”

“…The doses of bacteriophages used in this study were calculated as described before [10]. Briefly, the A549 cell line was either preincubated or coincubated with T4 or A5/80 phages in serial tenfold dilutions in cell culture maintenance medium, ranging from 1.47 × 10 3 to 1.47 × 10 9 PFU/mL (T4 phage) or 1.0 × 10 3 to 1.0 × 10 9 PFU/mL (A5/80 phage).…”

“…Our preliminary results showed that T4 phage preparation can inhibit infections by human type 5 adenovirus (HAdV-5) of A549 cells [10]. While coxsackievirus-adenovirus receptor (CAR) is the main protein bound by HAdV-5 at the adsorption step, the beta3 and beta5 integrins are utilized by the virus for cellular entry; moreover, in cells lacking CAR, integrins also act as adsorption receptors for the adenoviruses [11].…”

Phages and Immunomodulation

“…Some eukaryotic viruses can invade and replicate in platelets causing thrombocytopenia which is common in patients with viral infections [62]. Our findings on phage interference with adhesion and replication of some viruses [63] combined with the observations made in patients on phage therapy in whom some minor fluctuations in platelet counts could be noted [52] as well as the data summarized above, suggest that further studies are needed to shed light on phage interactions with platelets, with potential practical implications for the development of novel therapies.…”

“…The other mechanism may be the direct competition of phages with viruses for cellular receptors for viral cell entry [74]. Recently, we have provided data to support the latter option: T4 phage was found to significantly downregulate both the adsorption and replication of human adenovirus in a dosedependent manner [63]. These data indicate that T4 can inhibit infection by the eukaryotic virus, however, further studies are needed to determine if the phage may be considered a novel antiviral agent.…”